Mast cells are well-recognized for their role in innate and acquired immunity. Activation of mast cells by allergens and other stimuli leads to the release and de novo generation of a variety of airway inflammatory mediators including histamine, cysteinyl leukotrienes, prostaglandins, cytokines and enzymes such as tryptase. In asthma, mast cell-derived products can affect significant changes in airway architecture due to the close anatomical proximity of mast cells within the bronchial walls and adjacent blood vessels. Mast cell mediator release results in immediate bronchoconstriction as well as recruitment of other inflammatory cell types responsible for chronic airway inflammation that may ultimately lead to irreversible airway remodeling.
Study of human mast cell activation is limited by availability of few mast cell lines and their need for exogenous recombinant cytokines. Until 7 years ago, the only human cell culture available to researchers for study of mast cell biology was “human mast cell leukemia cells” termed HMC-1. One key limitation of HMC-1 is inconsistent ability to degranulate likely secondary to variable expression of the FceR1 alpha subunit. More recently, a second human mast cell line (LAD2) was described that more closely resembles characteristics of fully differentiated mature mast cells. LAD2 possesses the ability to consistently degranulate in response to IgE-mediated stimuli, as it expresses a complete FceR1 on its surface. Although LAD 2 represents a dramatic improvement over HMC-1 as a research tool to study mast cell biology, limitations include the requirement of costly exogenous cytokines to maintain the culture, and a neoplastic phenotype as the cells originated from a patient with mast cell sarcoma.